EP0743922A1 - Stabilisierte orthokieselsäure enthaltende zubereitung sowie biologische zubereitung - Google Patents

Stabilisierte orthokieselsäure enthaltende zubereitung sowie biologische zubereitung

Info

Publication number
EP0743922A1
EP0743922A1 EP95907143A EP95907143A EP0743922A1 EP 0743922 A1 EP0743922 A1 EP 0743922A1 EP 95907143 A EP95907143 A EP 95907143A EP 95907143 A EP95907143 A EP 95907143A EP 0743922 A1 EP0743922 A1 EP 0743922A1
Authority
EP
European Patent Office
Prior art keywords
preparation
stabilizing agent
silicic acid
silicon
ortho silicic
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
EP95907143A
Other languages
English (en)
French (fr)
Other versions
EP0743922B1 (de
Inventor
Stefan Raymond Bronder
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Bio Minerals NV
Original Assignee
Bio Pharma Sciences BV
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Bio Pharma Sciences BV filed Critical Bio Pharma Sciences BV
Publication of EP0743922A1 publication Critical patent/EP0743922A1/de
Application granted granted Critical
Publication of EP0743922B1 publication Critical patent/EP0743922B1/de
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C01—INORGANIC CHEMISTRY
    • C01B—NON-METALLIC ELEMENTS; COMPOUNDS THEREOF; METALLOIDS OR COMPOUNDS THEREOF NOT COVERED BY SUBCLASS C01C
    • C01B33/00—Silicon; Compounds thereof
    • C01B33/113—Silicon oxides; Hydrates thereof
    • C01B33/12—Silica; Hydrates thereof, e.g. lepidoic silicic acid
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/20—Inorganic substances, e.g. oligoelements
    • A23K20/28—Silicates, e.g. perlites, zeolites or bentonites
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients

Definitions

  • Silicon is an essential trace element for plants, animals and humans. In a watery environment silicon is initially present as ortho silicic acid which is quickly converted by polycondensation to polysilicic acid, which transposes into a colloidal solution and gels. Ultimately, insoluble silicates are formed.
  • ortho silicic acid is the most important metabolite for organic silicon compounds.
  • Water glass sodium ortho silicate is the usual source of ortho silicic acid, which however hydrolyses after oral administration to mammals and forms insoluble and non-absorbable gels through polycondensation.
  • Organic silicon compounds such as alcohol esters, such as ethyl ortho silicate and glycol ortho silicate, cannot be used in biological systems because of the poor solubility and the low resistance to hydrolysis, but above all because of the unacceptable toxicity.
  • silicon has a positive biological effect on nails, hair, skin, teeth, collagen, connective tissue, bones, encourages cell generation, stimulates the immune system against infections and toxins and inhibits degenerative (ageing) -processes .
  • the present invention is based on the insight that if ortho silicic acid is formed in the presence of a stabilizing agent, polycondensation is inhibited and even avoided and, furthermore, o rganic silicon compounds substantially do not occur.
  • a first aspect of the present invention therefore relates to a oreoaraticn comorisin ⁇ ortho silicic acid which is stabilized with a stabilizing agent and is substantially free of organic silicon compounds.
  • a second aspect of the present invention relates to a method for preparing a preparation as according to claims 1-7, which comprises of: i) providing a solution containing a stabilizing agent; ii) dissolving an inorganic silicon compound in the solution containing the stabilizing agent and iii) hydrolyzing the silicon compound to ortho silicic acid.
  • a third aspect of the present invention relates to a biological preparation containing a preparation according to claims 1-7, and/or a preparation prepared according to claims 8-13, and a pharmacologically acceptable diluent.
  • the biological preparation according to the invention can be used for: chronic infections with destruction of the mucous membranes: forms of sinusitis and ulcers. problems with connective tissues, arteriosclerosis, bone and tendon problems, gynaecology (fibroids, polycystic adenopathy) ; and the growth of children: children with recurrent infections with overload of the lymphatic system.
  • the stabilization using a stabilizing agent preferably takes place with stabilizing agents containing a nitrogen atom with a free electron pair which forms a complex with the silanol groups of the ortho silicic acid.
  • Quaternary ammonium compounds are preferably used, for instance tetra-alkyl compounds, wherein each alkyl group contains for instance 1-5 carbon atoms, in particular methyl and ethyl groups.
  • Very highly recommended are trialkylhydroxyalkyl compounds, wherein the hydroxy group is preferably methanol or ethanol .
  • Choline has been found very suitable, which is further recommended in that it provides the option of the stabilizing agent also forming the solution for the ortho silicic acid, and an inert solvent can therefore be omitted.
  • stabilizing agent is an amino acid, such as proline and serine. Serine enhances uptake in the stomach and gives additional stability.
  • Starting point for the preparation of the ortho silicic acid-comprising preparation is a solution containing the stabilizing agent, wherein an inert solvent can be used. Incorporated in this solution is an inorganic silicon compound which hydrolyses under the influence of water to ortho silicic acid, which is immediately stabilized by the stabilizing agent that is present.
  • the solution containing the stabilizing agent can initiate the hydrolysis immediately after addition of the inorganic silicon compound.
  • a solution containing a stabilizing agent in which no hydrolysis can take place until after the addition of a hydrolyzing agent, such as water.
  • choline is used as stabilizing agent it can be converted to choline hydrochloride using dry hydrochloric acid.
  • this liquid stabilizing agent can be incorporated the inorganic silicon compound, such as a silicon halogenide, particularly silicon tetrachloride.
  • the hydrolysis of the inorganic silicon compound to ortho silicic acid takes place.
  • the silicic acid formed in situ is subsequently stabilized by forming a complex with the stabilizing agent.
  • the stabilizing agent only forms a complex and does not enter into a reaction, particularly an esterifying reaction, with the ortho silicic acid.
  • no organic silicon compounds are created which have an inherent toxicity, are absorbed in the stomach and enter the blood circulation.
  • the ortho silicic acid-comprising solution can if desired be partially neutralized by adding a base, such as a lye, particularly sodium hydroxide. Neutralization can take place to a pH smaller than 4, in particular smaller than 3, in general to a pH lying in the range of 1-3, whereby any polycondensation of ortho silicic acid is substantially avoided.
  • a further purification of the preparation can take place, for instance through absorption of contaminants on active carbon, optionally followed by filtration.
  • the content of hydrolyzing agent, particularly water can be reduced by removing the hydrolyzing agent, for instance through distillation, whereby a constant viscosity is achieved if use is made of choline as the stabilizer.
  • Preparations then result with a silicon content generally of 1% by weight, preferably of about 4% by weight, such as 8% by weight .
  • a very acceptable preparation contains 3-5% by weight of silicon, 70% by weight of choline hydrochloride and the rest water. The pH of this preparation lies within the range 1-3.
  • Biological preparations can be manufactured from this prepared preparation for the purpose of administering ortho silicic acid to plants, animals and humans, whereby the bio-availability of silicon is greatly improved.
  • the above prepared solution can be administered as biological preparation as such, for instance as nail tincture.
  • a usage of 0.5 ml of a 2% Si-solution per day for three weeks caused a fungal infection to disappear (3 patients) , where treatment with ketonazols did not render any improvement.
  • an edible acid such as malic acid
  • a preparation results which is very suitable for administering to horses.
  • a solid carrier for instance cattle feed, cattle feed pellets can be pressed therefrom which contain ortho silicic acid in stabilized form for administering silicon to cattle. If sugar/maltose is used as solid carrier, tablets and gels can be formed therefrom.
  • glucuronic acid buffer a preparation on a cream basis can be formed wherein the pH is less than 4, which creams are suitable for local cutaneous application.
  • diluents can be used in order to obtain a preparation for biological application.
  • diluents contain lower alkanols, such as ethanol, dichloromethane, ethyl acetate, glycerine and oolvalcohols .
  • Choline hydrochloride (UCB) is dried under vacuum (100°C/6 hours) .
  • the choline hydrochloride is treated with dry hydrochloric acid.
  • Silicon hydrochloride (1 mol per mol) is added to the formed choline solution at a temperature which is kept below 40°C.
  • water ice/ice water
  • the solution containing the ortho silicic acid is subsequently neutralized by adding sodium hydroxide wherein cooling takes place to a temperature below 0°C.
  • the pH neutralization amounts to about 1.3.
  • a purification over active carbon is then performed, followed by filtering off the formed precipitate and the active carbon.
  • Neutralization is subsequently carried out to a pH of 2.7 - 3.0.
  • the preparation is stable for more than two years when stored at room temperature.
  • the biological preparation contains 3% by weight silicon in the form of ortho silicic acid, 70% by weight choline hydrochloride, the rest water and a pH of 2.7 - 3.0. This liquid is suitable for oral and cutaneous administering.
  • the oiological preparation as prepared above is mixed with cattle feed which ultimately contains silicon as ortho silicic acid in a concentration of 0.001-0.005% by weight. This mixture can be pressed to pellets which are administered to cattle.
  • FORMULATION EXAMPLE C The preparation A is mixed with sugar and/or maltose which is pressed to tablets containing silicon in the form of ortho silicic acid at a content of 0.1-0.2% Si by weight.
  • a silicon-comprising cream is prepared as follows.
  • a fat phase containing Imwitor 960 (H ⁇ ls) 7%, Miglyol 812 10%, Softigon 701 (H ⁇ ls) 2%, Marlowet TA 25 (H ⁇ ls) 2%, Lanette N (Henkel) 4%, Isopropylmyristate 3%, a water phase containing Inositol 0.2%, Gluconate buffer 0.05 M, pH 3.8 ad 100, Glycerol 10% and the preparation A, as well as a perfume.
  • the fat phase is melted at 80°C, whereafter the water phase, also heated to 80°C, is admixed, followed by cooling.
  • the preparation A and perfume are added.
  • the cream eventually contains 0.01-0.05% by weight silicon as ortho silicic acid.
  • Flavourings can be added if desired, for instance by dilution (1:30) in a 0.01 M citrate buffer (pH 3.5-3.8) and by adding a flavouring (raspberry and the like) .

Landscapes

  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Inorganic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Polymers & Plastics (AREA)
  • Public Health (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Animal Husbandry (AREA)
  • Zoology (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Food Science & Technology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Cosmetics (AREA)
  • Silicon Compounds (AREA)
  • Fodder In General (AREA)
EP95907143A 1994-02-07 1995-02-07 Stabilisierte orthokieselsäure enthaltende zubereitung sowie biologische zubereitung Expired - Lifetime EP0743922B1 (de)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
NL9400189 1994-02-07
NL9400189A NL9400189A (nl) 1994-02-07 1994-02-07 Gestabiliseerd orthosiliciumzuur bevattend preparaat, een werkwijze voor het bereiden daarvan en een biologisch preparaat.
PCT/NL1995/000054 WO1995021124A1 (en) 1994-02-07 1995-02-07 Stabilized orthosilicic acid comprising preparation and biological preparation

Publications (2)

Publication Number Publication Date
EP0743922A1 true EP0743922A1 (de) 1996-11-27
EP0743922B1 EP0743922B1 (de) 1998-07-22

Family

ID=19863801

Family Applications (1)

Application Number Title Priority Date Filing Date
EP95907143A Expired - Lifetime EP0743922B1 (de) 1994-02-07 1995-02-07 Stabilisierte orthokieselsäure enthaltende zubereitung sowie biologische zubereitung

Country Status (12)

Country Link
US (1) US5922360A (de)
EP (1) EP0743922B1 (de)
JP (1) JP3808499B2 (de)
CN (1) CN1049195C (de)
AT (1) ATE168662T1 (de)
AU (1) AU698236B2 (de)
CA (1) CA2181825C (de)
DE (1) DE69503604T2 (de)
DK (1) DK0743922T3 (de)
ES (1) ES2119388T3 (de)
NL (1) NL9400189A (de)
WO (1) WO1995021124A1 (de)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2526954A1 (de) 2011-05-26 2012-11-28 Dexsil Labs Bioverfügbarer Siliziumkomplex, sein Herstellungsverfahren und sein Einsatz
EP3549578A1 (de) 2018-04-06 2019-10-09 Bio Minerals N.V. Kieselsäureformulierung und verwendung davon
EP3650011A1 (de) 2018-11-09 2020-05-13 Bio Minerals NV Wasserlösliches siliciumhaltiges granulat
US11878031B2 (en) 2018-10-05 2024-01-23 Bio Minerals N.V. Silicic acids for use in the treatment of periodontitis

Families Citing this family (27)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2116810T5 (es) † 1995-05-30 2002-12-16 Oreal Utilizacion de acido silicico coloidal para reforzar las materias queratinicas.
FR2799758B1 (fr) 1999-10-15 2002-05-17 Exsymol Sa Complexe a base d'acide orthosilicique biologiquement assimilable, se presentant sous forme solide, stable et concentree, et procede de preparation
EP1110909A1 (de) * 1999-12-24 2001-06-27 Bio Minerals N.V. Verfahren zur Herstellung von Orthokieselsäure, sowie nach dem Verfahren hergestellte Kieselsäure und ihre Verwendung
EP1371289A1 (de) * 2002-03-20 2003-12-17 Bio Minerals N.V. Cholin-Kieselsäure-Komplex
US9078465B2 (en) 2002-03-20 2015-07-14 Bio Minerals N.V. Choline-silicic acid complex with osmolytes and divalent trace elements
EP1391426A1 (de) * 2002-08-12 2004-02-25 Bio Minerals N.V. Verfahren zur Herstellung eines kieselsäureenthaltenden Extrudates, das Extrudat, dessen Verwendung und eine das Extrudat enthaltende pharmazeutische Zusammensetzung
WO2009052090A2 (en) 2007-10-15 2009-04-23 7 Oaks Pharmaceutical Corporation Silicate containing compositions and methods of treatment
GB0805279D0 (en) 2008-03-20 2008-04-30 Univ Nottingham Trent Food supplement
WO2009127256A1 (en) 2008-04-17 2009-10-22 Jisbrey, S.A Hydronium stabilized and dissoluble silicic acid nanoparticles: preparation, stabilization and use
CZ2008841A3 (cs) 2008-12-23 2010-07-28 Agra Group, A.S. Pivo a nápoje na bázi piva a zpusob úpravy obsahu polyfenolu a kremíku v nich
WO2011010188A1 (en) * 2009-07-23 2011-01-27 Societe Anonyme Des Eaux Minerales D'evian "S.A.E.M.E" A process for producing water enriched with natural orthosilicic acid
GB0913255D0 (en) 2009-07-30 2009-09-02 Sisaf Ltd Topical composition
EP2509414B1 (de) 2009-12-09 2017-08-09 Barlaa B.V. Mikrokolloidale kieselsäure-/borsäurezusammensetzung und verfahren zur herstellung einer bioverstärkenden lösung und pulver
PL2371220T3 (pl) * 2010-03-31 2015-04-30 Taminco Stabilizowany, biologicznie dostępny roztwór rozpuszczalnego krzemianu
WO2012032364A1 (en) 2010-09-06 2012-03-15 Creogen D.O.O. Stabilized solution of ortho-silicic acid based on salicylic acid as effective inhibitor of its polymerization, its preparation and use
WO2012035364A1 (en) 2010-09-15 2012-03-22 Creogen D.O.O. Stabilized solution of ortho-silicic acid, its preparation and use
PL403902A1 (pl) * 2013-05-15 2014-11-24 Przedsiębiorstwo Intermag Spółka Z Ograniczoną Odpowiedzialnością Preparat krzemowy o właściwościach stymulujących rozwój roślin, sposób wytwarzania preparatu krzemowego stymulującego rozwój roślin i jego zastosowanie
GB201402669D0 (en) * 2014-02-14 2014-04-02 Medical Res Council Stabilised silicate compositions and their uses
GB201402672D0 (en) 2014-02-14 2014-04-02 Medical Res Council Materials and methods relating to stabilised polymeric silicate compositions
EP3141244B1 (de) 2015-09-09 2023-11-29 Cindro Holding BV Emulsionen mit kieselsäure
SG10202100422VA (en) 2016-08-10 2021-02-25 Res & Innovation Uk Compositions comprising nanosilica particles and their use in methods of activating t lymphocytes for therapy
WO2019150382A1 (en) * 2018-01-30 2019-08-08 Privi Life Science Private Limited A method for preparation of othro silicic acid for agriculture
GB201904336D0 (en) 2019-03-28 2019-05-15 Sisaf Ltd A delivery system
JP2020180107A (ja) * 2019-04-25 2020-11-05 有限会社グリーン化学 珪酸コリン水溶液の製造方法
CN114886917B (zh) * 2022-05-09 2023-07-18 国科温州研究院(温州生物材料与工程研究所) 一种用于治疗主动脉夹层和主动脉瘤的离子试剂及制备方法与应用
WO2024028039A1 (en) 2022-08-02 2024-02-08 Barlaa B.V. Stabilised silicic acid solutions
WO2024047235A1 (en) * 2022-09-01 2024-03-07 Barlaa B.V. Silicic acid for improving milk production in dairy livestock

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Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2526954A1 (de) 2011-05-26 2012-11-28 Dexsil Labs Bioverfügbarer Siliziumkomplex, sein Herstellungsverfahren und sein Einsatz
EP3549578A1 (de) 2018-04-06 2019-10-09 Bio Minerals N.V. Kieselsäureformulierung und verwendung davon
WO2019193200A1 (en) 2018-04-06 2019-10-10 Name: Bio Minerals N.V. Silicic acid formulation and use thereof
US11878031B2 (en) 2018-10-05 2024-01-23 Bio Minerals N.V. Silicic acids for use in the treatment of periodontitis
EP3650011A1 (de) 2018-11-09 2020-05-13 Bio Minerals NV Wasserlösliches siliciumhaltiges granulat
WO2020094886A1 (en) 2018-11-09 2020-05-14 Bio Minerals Nv Water soluble silicon-containing granulate

Also Published As

Publication number Publication date
WO1995021124A1 (en) 1995-08-10
DE69503604T2 (de) 1998-11-26
ES2119388T3 (es) 1998-10-01
DE69503604D1 (de) 1998-08-27
CN1049195C (zh) 2000-02-09
NL9400189A (nl) 1995-09-01
DK0743922T3 (da) 1999-04-26
AU698236B2 (en) 1998-10-29
AU1545995A (en) 1995-08-21
CN1143354A (zh) 1997-02-19
US5922360A (en) 1999-07-13
EP0743922B1 (de) 1998-07-22
ATE168662T1 (de) 1998-08-15
CA2181825A1 (en) 1995-08-10
CA2181825C (en) 2005-07-05
JPH09508349A (ja) 1997-08-26
JP3808499B2 (ja) 2006-08-09

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